Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas. - Aix-Marseille Université Access content directly
Journal Articles Proceedings of the Royal Society B: Biological Sciences Year : 2016

Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas.

T. Vogwill
  • Function : Author
  • PersonId : 999119
R. Craig. Maclean
  • Function : Author
  • PersonId : 998019

Abstract

Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase (rpoB) across eight strains that span the diversity of the genus Pseudomonas We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across three strains of Pseudomonas Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds.
Fichier principal
Vignette du fichier
rspb20160151.pdf (1019.04 Ko) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-01444160 , version 1 (13-06-2023)

Identifiers

Cite

T. Vogwill, Mila Kojadinovic, R. Craig. Maclean. Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas.. Proceedings of the Royal Society B: Biological Sciences, 2016, 283(1830), ⟨10.1098/rspb.2016.0151⟩. ⟨hal-01444160⟩

Collections

CNRS UNIV-AMU
37 View
2 Download

Altmetric

Share

Gmail Facebook X LinkedIn More